Nobuhiro Tanabe1, Keiichi Fukuda2, Hiromi Matsubara3, Norifumi Nakanishi4, Nobuhiro Tahara5, Satoshi Ikeda6, Takuya Kishi7, Toru Satoh8, Ken-Ichi Hirata9, Teruo Inoue10, Hiroshi Kimura11, Yoshiaki Okano12, Osamu Okazaki13, Masataka Sata14, Ichizo Tsujino15, Shuichi Ueno16,17, Norikazu Yamada18, Atsushi Yao19, Takayuki Kuriyama20. 1. Department of Respirology, Graduate School of Medicine, Chiba University. 2. Department of Cardiology, Keio University School of Medicine. 3. Director of Entire Medical Departments, National Hospital Organization Okayama Medical Center. 4. Department of Cardiology, Osaka Namba Clinic. 5. Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine. 6. Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences. 7. Department of Cardiology, Graduate School of Medical Sciences, International University of Health and Welfare. 8. Department of Cardiovascular Medicine, Kyorin University Hospital. 9. Cardiovascular Medicine, Kobe University Graduate School of Medicine. 10. Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine. 11. Respiratory Disease Center, Fukujuji Hospital. 12. Department of Intermal Medicine, Hanwa Dai-ni Senboku Hospital. 13. Department of Cardiology, National Center for Global Health and Medecine. 14. Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences. 15. The First Department of Medicine, Hokkaido University School of Medicine. 16. Department of Internal Medicine Division of Cardiovascular Medicine, Jichi Medical University School of Medicine. 17. Ueno Clinic. 18. Department of Cardiology, Kuwana City Medical Center. 19. Department of Cardiovascular Medicine, The University of Tokyo Hospital. 20. Kuriyama Clinic.
Abstract
BACKGROUND:Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results: This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index. CONCLUSIONS:Selexipag treatment improved pulmonary hemodynamics in Japanese patients withCTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).
RCT Entities:
BACKGROUND:Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results: This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index. CONCLUSIONS:Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).